Cancer is the top cause of death in Japan. Approximately 350,000 patients die of cancer every year, and cancer is still a serious disease nowadays. The primary techniques for cancer treatment that have been established are surgical resection, anti-cancer drug treatment, and radiation treatment. However, such treatment strategies are problematic in terms of, for example, recurrence, decline in quality of life (QOL), and lack of treatment options in the case of advanced-stage cancers that cannot be treated with the strategies described above.
Cancer immunotherapy (cancer vaccines) has been expected as a novel therapeutic technique for a long period of time, and clinical studies on peptide vaccines for cancer treatment were initiated throughout the world in 1990 when epitope peptides in human tumor antigens became identifiable. According to the results of analysis of clinical studies conducted via administration of a peptide alone or in combination with other agents, however, the response rate is as low as 2.7% among 1,000 or more cases (Rosenberg S A et al., Nature Med., 2004, 10 (9): 909-15). Thus, difficulty in practical application has been pointed out.
Meanwhile, clinical studies involving the use of particular peptide vaccines for cancer treatment have been underway for a long period of time in Japan, and the achievements of such studies have gradually been articulated. In recent years, a strategy of administration of a multiple cancer peptides instead of a single type of cancer peptide has been attempted, with the aim of improving the outcome for treatment. For example, the HLA type and specific immune responses of a patient are examined in advance, so as to implement a tailor-made cancer treatment using peptide vaccines comprising selecting multiple adequate peptides to be administered, and safety and anti-tumor effects thereof have been verified. Through administration of tailor-made peptide vaccines alone or in combination with anti-cancer drugs, more specifically, excellent clinical effects and safety have been achieved in cases of brain tumor, uterine cervix cancer, prostate cancer, and pancreatic cancer (Terasaki, M. et al., J. Clin. Oncol., 2011, 29 (3): 337-44; Noguchi, M. et al., Cancer Immunol. Immunother., 2010, 59 (7): 1001-9; Yanagimoto, II. et al., Cancer Sci., 2007, 98 (4): 605-11).
The cell-mediated immunity consisting of epitope specific cytotoxic T lymphocytes (hereafter, abbreviated as “CTL”), which are considered to be major effector cells in cancer treatment using peptide vaccines, is HLA-restrictive. Accordingly, development of peptide vaccines for cancer treatment exclusively targeting patients with a particular HLA type, and specifically an HLA-A2 or HLA-A24 type, has been attempted because of the large number of patients therewith.
However, Japanese people with such two HLA types account for approximately 40% and 60%, respectively (Sette, A. et al., Immunogenetics, 1999, 50 (3-4): 201-12). Disadvantageously, patients with other HLA types cannot gain benefits from peptide vaccines for cancer treatment. In addition, the time of initiation of treatment would be postponed because of HLA typing performed prior to the initiation of treatment, and it would increase the burden on patients. Accordingly, research and development of peptide vaccines for cancer treatment that are applicable to all cancer patients without HLA typing are desired.
Regarding cancer treatment using peptide vaccines, in addition to activations of CTLs for cell-mediated immunity, inductions of production of immunoglobulins known as the humoral immunity is known to be attributable to survival benefit (Noguchi, M. et al., Cancer Biol. Ther., 2011, 10 (12):1266-79).